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Introduction

Peripheral neuropathy is not just a common neurological problem, but also a common medical problem (for general physicians and general practitioners).  If truth be told, most neurologists do not find the assessment and investigation of peripheral neuropathy terribly rewarding.  That said, there are some important forms of neuropathy, above and beyond the common ones, which are definitely worth a little space on a neurology undergraduate teaching curriculum.

In basic terms, peripheral neuropathies arise from damage to either the insulation of the peripheral nerve (myelin) or to the central cable (axon).  In practice, both are often affected, although it is very difficult to tell this without resorting to complex neurological investigations.

The predominant symptoms depend very much on which types of peripheral nerve are targeted.

It is beyond the scope of this webpage, or the enthusiasm of the author, to provide you with an exhaustive list of causation.  Hopefully, I can provide you with enough information to make a confident clinical diagnosis of a peripheral neuropathy, should you encounter one, and feel able to initiate a plan of investigation.

How does it present?

As previously mentioned, the main symptoms depend very much on which peripheral nerves are damaged.  There are three main types of peripheral nerve:

• Sensory – damage to these nerves leads to numbness, tingling, hypersensitivity to touch, pain etc.
• Motor –  damage to these nerves leads to weakness and muscle wasting
• Autonomic –  damage to these nerves leads to disordered sweating, orthostatic hypotension and bladder/ bowel dysfunction

Obviously, if symptoms are purely “sensory”, then we refer to this as a sensory neuropathy.  If symptoms are purely “motor”, then we refer to this as a motor neuropathy.  If there is a mixture of sensory and motor features, then we refer to this as a “sensorimotor” neuropathy.

Who said neurology was difficult?

In addition to symptoms, one can also classify neuropathies according to the speed with which they develop.  Having a “top five” for each of these categories can be extremely helpful when trying to get to the bottom of a clinical case.  As a general rule,  the more rapidly a neuropathy presents, the more likely we are to identify an underlying cause and be able to initiate a specific management plan.

We tend to subdivide the presentations as follows:

• hyperacute (24+ hours)
• acute (< 4 weeks)
• subacute (1-3 months)
• chronic (> 3 months)

The pattern of nerve damage is also worth trying to get a feel for.  The three main categories, in terms of pattern, are as follows:

Diffuse

In this situation a wide number of nerves are involved, both in the upper and lower limbs.  Sometimes, cranial nerves and nerves to the respiratory muscles are also targeted.  Diffuse neuropathies, particularly when they present quickly, are a neurological emergency.

Multi-focal

This pattern can sometimes be a little misleading.  What we really mean is that individual nerves are picked off by the pathological process.  Initially, presentation is therefore patchy.  Over time, if severe enough, a multifocal presentation can become diffuse.

Focal

This usually refers to a single nerve, such as an ulnar or median neuropathy.  We will talk about some of the more useful focal neuropathies later.

Just to further confuse matters, some textbooks and neurologists (who like to think of themselves as walking textbooks) will refer to a neuropathy based on the size of the nerve fibre affected.  This terminology is really only relevant for sensory fibres.

• large fibres –  these are fast-conducting fibres, sending joint position sense and vibration information into the spinal cord.  Damage to these fibres leads to vibration and proprioceptive loss,  and a sense of unsteadiness, particularly on uneven ground, or with the eyes shut.
• small fibres – these are slow-conducting fibres, mediating pain and temperature sensation. Damage here, rather unsurprisingly, leads to pain, tingling and an inability to sense skin temperature.

When taking a history from a patient with a potential neuropathy, the social and family history become extremely important.  Concomitant medical conditions can be associated with neuropathic damage, as can excessive alcohol use.  A variety of medications can also cause nerve damage and, without taking a detailed history, you may well miss this.

Occupation may also be relevant.

Lastly, there are a number of genetic causes of neuropathy and these are not quite as rare as you might think. We will mention some of the more common ones in due course.

How does it behave?

It is almost impossible to provide a single answer to this question.  Some neuropathies behave in an indolent and fairly benign fashion.  Whilst causing sensory and motor problems, they can be managed on an outpatient basis without too much difficulty.  Others, however, can present in a devastating and life-changing fashion and it is therefore vital to get the most detailed picture of the neuropathy at the point of presentation.

We will now go on to discuss a number of the patterns and presentations already mentioned, in a little more detail.

Focal neuropathies

Facial palsy (Bell’s)

Unilateral facial palsy is perhaps one of the more common presentations.  Most GPs and hospital physicians will have come across this problem.  Often referred to as “Bell’s Palsy”, it presents as a fairly abrupt-onset unilateral facial weakness, typically involving the forehead as well.

It is worth mentioning, however, that a partial facial palsy can seem to spare the forehead, causing  diagnostic uncertainty.  Many patients report a “numb” face.  I suspect that, what most people really mean, is that the face does not feel right.  Unless there is objective evidence of reduction in light touch sensation, I would not tend to get too hung up on a reported sensory abnormality, in the context of an obvious facial palsy.
There is little point in testing corneal reflex, as the patient will often be unable to blink.  You could, however, as the patient if they can feel the cotton wool touching the front of the eye; they usually can.  It is also very common, in a Bell’s palsy presentation, for patients to have pain behind the ear.

If neurologists ever give you a hard time for admitting a patient with Bell’s palsy, or ringing them up, it is worth remembering that most neurology registrars have admitted several such patients in the course of their training.  They may not wish to admit this to you, but they do feel your pain!

Treatment of an uncomplicated Bell’s palsy presentation is prompt administration of high-dose oral steroids, soon as possible after the onset of symptoms (preferably within 48 hours).  There is no role for acyclovir, unless vesicles are seen in the ear, on examination.  Perhaps more important than the steroids is appropriate advice on eye care. If you can’t close your eye when asleep, the surface of the eye will dry out and ulcerate.  Lubricating eye drops, ophthalmological assessment and nocturnal eye patching may all be required.

Carpal tunnel (median nerve palsy)

Carpal tunnel syndrome is an extremely common presentation.  Symptoms are most prominent at night and patients will typically describe pain in the hand and forearm and a tingling feeling affecting the thumb, index and middle finger.  Often, symptoms are bilateral.

The majority of patients have a sensory presentation only. Conservative advice and management with nocturnal splinting may suffice in this setting. Some will also develop thumb weakness and, if this is the case, then prompt assessment and surgical treatment are required.

It is not always necessary to undertake specific investigations but, if the presentation is unusual, then nerve conduction studies can be undertaken. It is usually also worth checking thyroid function.

Radial palsy

Radial nerve palsy is sometimes referred to as the “Saturday night palsy”. This is because the most common cause of pressure damage to the radial nerve is from an awkward sleeping position.  Medical students have, perhaps unfairly, been described as prime candidates for the development of this kind of neurological presentation, due to their propensity for falling asleep, whilst inebriated, in an uncomfortable chair.

The presentation is usually fairly dramatic – acute-onset wrist drop, with weakness of hand muscles due to the wrist drop itself.  If carefully tested, with a hand on a flat surface, then the ulnar nerve function can easily be demonstrated as normal.

The radial nerve has very little in the way of sensory function.  Sometimes, patients will mention a patch of numbness on the dorsum of the hand.

A wrist splint is very helpful in supporting hand function, until the nerve gradually repairs itself.

Ulnar palsy

Ulnar nerve palsy tends to occur due to pressure at the elbow.  We are all familiar with hitting our “funny bone”.  This leads to a unpleasant tingling in the little and ring finger of the affected hand.  The ulnar nerve is very vulnerable at this point in it’s pathway.  Endless revision for medical finals, whilst propping your weary head on your hands, and leaning your elbows on the table can easily lead to ulnar compression.

Because the ulnar nerve supplies many of the intrinsic muscles of the hand, ulnar nerve palsies are actually extremely disabling. Look out for wasting on the muscles although, if this has occurred, recovery will be poor – the point is to get it sorted before this happens.

There are obviously other points in the nerve pathways where damage can occur.  Whilst it might be quite useful for a consultant neurologist to know this kind of information, I can conceive of little practical use for medical students and junior doctors.

Investigation with nerve conduction studies can be extremely helpful in trying to localise the site of the problem.

Lateral cutaneous nerve of the thigh (meralgia paresthetica)

Compression of the lateral cutaneous nerve of the thigh is actually very common.  The main site of compression is the inguinal ligament.

The diagnosis is usually straightforward, with patients complaining of tingling, numbness and pain on the outer aspect of the thigh.

Principal risk factors are obesity, pregnancy and diabetes.

Common peroneal

Common peroneal nerve palsy usually occurs as the nerve wraps around the head of the fibula.  “Kinky” boots and below knee plaster of Paris (POPs) can be the cause, although kneeling awkwardly for long periods of time for one’s profession can also be causative.  We occasionally see it in the post-partum period, particularly if a patient has been in labour for a long time.

Clinically, patients present with a high-stepping gait, and a tendency to catch their foot on steps and uneven ground.  Careful testing should reveal weakness of ankle eversion and dorsiflexion, but normal plantar flexion and inversion.  The ankle jerk should be preserved (unlike in compression of the L5/S1 nerve root, which also causes a foot drop, and is part of the differential diagnosis).

Multifocal

Vasculitic

If you asked most neurologists which form of neuropathy worries them the most, then a large number would opt for a vasculitic neuropathy.  Although uncommon, it is typically diagnosed late, when much irreversible damage has already been done.  You will therefore forgive me if I put it high up the list of things to know about.

Essentially, patients present with fairly abrupt-onset weakness and sensory disturbance, in the territory of a particular peripheral nerve (ulnar, common peroneal, radial).  Usually the onset is also associated with severe neuropathic pain.

The neuropathy can progress quite quickly, picking off nerves left, right and centre.  If not treated promptly, this can lead to severe neurological disability.

Usually, vasculitic neuropathy is caused by an underlying immune-mediated disorder.  The list of these is long and complex.  The bottom line is, because the disorder is potentially reversible, but progresses rapidly, if you suspect a vasculitic neuropathy then you need to pick up the phone to your local neurologist – friendly or otherwise – and get your patient on high-dose immunosuppression PDQ (pretty damn quick).

Brachial neuritis

Brachial neuritis is a particularly unpleasant focal neuropathy, this time targeting the brachial plexus in the upper limb.  A similar process can affect the plexus in the lower limb, although this is less common.

Usually, patients have severe pain for 1-2 weeks, in the region of the shoulder.  As the pain, which is usually pretty nasty, resolves, wasting and weakness then begin to dominate the clinical picture.  The wasting can actually be quite profound and winging of the scapula is not uncommon.
Diagnosis is usually pretty straightforward, as one arm looks pretty knackered (to use complex neurological chatter) whilst the other one is fine.

Recovery can take months, or even years.  The cause is unclear.

Neuralgic amyotrophy

Diabetic patients seem to be particularly prone to this problem.  Again, it tends to present in either an acute or sub-acute fashion.  Like brachial neuritis, it can be painful.  Proximal weakness is the norm.  Usually, only one side of the lower limb plexus is affected although, in rare circumstances, it can recur in the previously unaffected side at a later date.

This presentation is very different from the normal peripheral nerve problems seen in diabetes, which are typically distal, rather than proximal.

Diffuse

The diffuse neuropathies are probably the most common. They conform to the textbook stereotype of a neuropathy, typically presenting with “glove and stocking” sensory disturbance, if sensory disturbance is part of the presentation, and a distal weakness, if weakness is part of the presentation.

It is difficult to discuss diffuse neuropathy without a degenerating into an extremely tedious list of causes.  It can be helpful to try and spit them up depending on the rapidity with which they present.  This can prevent you from doing hundreds of pointless tests in every patient you meet.

Acute and hyper-acute neuropathies

The list of acute and hyper-acute neuropathies is mercifully short.  We have already touched on some of these in the discussion above.

Acute and hyper-acute neuropathies	Top Tips
GBS	Nasty, acute, mostly motor. Recovery the the norm but I tell my patients “GBS” stands for “Gets Better Slowly”
Miller Fisher Syndrome	Like GBS, and kinda is GBS, but classically causes facial palsies, oculomotor palsies, ataxia and areflexia. Weird, unpleasant but full recovery is typical
Porphyria (AIP)	Rare as the proverbial toothed hen. Sometimes triggered by medication. Motor only.
Diabetic amyotrophy	See above

Assuming that you are unlikely to ever meet a patient with acute intermittent porphyria, then that really just leaves us to discuss GBS.

GBS can present in a devastating fashion.  Typically, although it can cause some sensory symptoms, it is nearly always a mostly motor neuropathy.  Onset is often in the wake of a “viral” illness.  Diarrhoeal illness can also precede the presentation, as can (rarely) immunisation.

Weakness tends to progress over hours and days, reaching a nadir after about a week.  It is not unusual for diagnosis to be delayed until a crisis point has been reached.  Weakness tends to  ascend up the legs and into the upper limbs.  Cranial muscles can also be affected, leading to facial weakness and speech and swallowing problems.  If the respiratory muscles are also targeted ,then ventilatory failure can occur.

The following video shows a very severe presentation – even the eye muscles were affected. I’ll let Ken and Bev tell you more.

If you have a patient with suspected GBS, then tests of vital capacity, coupled with arterial blood gases, should be considered for any patient with subjective or objective respiratory symptoms.  If you wait until your patient is hypoxic and hypercarbic on a blood gas, you have waited far too long and your patient is about to go into respiratory arrest!

Getting an FVC on a busy medical ward is impossible, so try this instead - breath counts. Just ask the patient to take a deep breath in and start counting up from “1” in a normal voice. See how far they can get to in one breath. Try it yourself - you should make it to about 30 or 40. Granted, this all depends on the speed of counting, and you cant compare numbers between patients but, it the individual breath count is dropping steadily over the course of 24 hour period - WORRY!

Generally speaking, neurologists like to know about cases of potential GBS earlier rather than later.  The same can be said for intensive care specialists.

Investigation of a suspected case of GBS includes looking for potential infectious triggers.  In general, blood tests are not terribly helpful.  A lumbar puncture, if performed after a few days, can show an elevated CSF protein.  This suggests immune activity in the nerve roots, leading to a protein exudate into the CSF itself.  Ultimately, the diagnosis is best made using nerve conduction studies.  In addition to confirming the presence of a neuropathy, they can also help demonstrate whether the nerve damage is predominantly demyelinating, axonal or a mixture of both.

We tend to treat patients with intravenous immunoglobulin or plasma exchange.  Whilst by no means a “miracle”, the evidence does suggest that, if treated promptly, patients tend to spend less time in hospital.

Although most patients make a reasonable recovery, and many a complete recovery, this is not universally the case.  Mortality rates can be as high as 10%, usually due to complications of the need for ventilation and/or autonomic involvement.

Sub-acute neuropathies

Subacute neuropathies tend to present over weeks or months, rather than hours or days.  Sadly, as we move into this territory, we are looking at a much longer differential diagnosis.

It is worth mentioning para-neoplastic neuropathies in a little detail.  These can be quite aggressive and often act as an early-warning system for an underlying malignancy.  In an ideal world, prompt diagnosis and investigation would lead to definitive treatment of the underlying tumour.  One might then see a gradual resolution of the neuropathy.

In practice, detecting an occult malignancy can be extremely difficult, even if one suspects a para-neoplastic presentation.

In addition to CT scans of the whole body, SPECT scans etc.,  one can also undertake specific blood tests looking for para-neoplastic antibodies.  It is actually quite difficult to keep any of this information in your brain from more than 10 seconds; for this reason, I will spare you the list.  Suffice to say that, if you are pondering a possible para-neoplastic presentation, then a quick chat with Professor Google can be time very well spent (other search engines are available).

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a relatively uncommon, but treatable, chronic neuropathy.  It is sometimes thought of as the longer-acting version of GBS.  I am not sure that this analogy is quite correct, but it does provide one way of thinking about the condition.  It can actually present quite aggressively but, in most cases, neurological disability progresses over a number of months.  Almost any pattern of symptoms can be seen – proximal, distal, global, pyramidal – you name it.

Diagnosis can be very challenging.  A stack of blood tests, a lumbar puncture and nerve conduction studies are the norm.  Occasionally, we will even resort to a nerve biopsy.

The reason we go to all this trouble is that, if appropriately diagnosed, then the condition can be reversed or, at the very least, held in check.  We tend to use high-dose oral steroids, steroid-sparing immunosuppressants and intravenous immunoglobulin, either singly, or in combination.

There are a load of others, which I have popped into a table below. I just can’t face writing any more about neuropathies so you are on your own with this.

Subacute neuropathies	Top Tips
Paraneoplastic	Relentless, sometimes targeting the dorsal root ganglions, leading to profound sensory ataxia
CIDP	Presents in a variety of ways. Can be aggressive. Generally responds to immunotherapy
Vitamin deficiencies	For your exams, read B12. Also causes spinal cord damage, so presentations can be complicated. Can present aggressively, but this is very rare.
Drugs	Usually chemotherapy agents in this subacute setting
Toxins	Can’t think of any in the UK, off the top of my head!
Diabetic amyotrophy	See above
Vasculitic	See above

Chronic sensory neuropathies

Chronic sensory neuropathies are probably one of the most common ones that we see in the outpatient clinic.

Patients often complain of tingling and pain in their feet.  It is not unusual to hear patients comments that “it feels like I am walking on pebbles” for “it feels like I have crumpled up socks under my feet”.  Symptoms are often worse at night.

Examination reveals a reduction in light touch, pinprick in temperature sensation with a “stocking” distribution.  Sometimes, the ankle jerk is absent (in contrast to the knee-jerks).  Motor examination is typically normal.

As you can see from the table below, there are a number of things to consider in the history.  Investigation should be self-evident from a glance through the list.

Chronic sensory neuropathies	Top Tips
DM	What can I say? Common, common and common. Usually other “end organ” diabetic damage – eyes, kidneys
Alcohol	Need to take a careful alcohol history, and then at least double it! High MCV can tip you off to booze
Vitamin deficiencies	Again, B12 is the top culprit. Not that common these days – look for a large MCV on the FBC as a clue.
Drugs	Loads in this category – anti-epileptic, chemotherapy, amiodarone
Toxins	Rare in the UK. Lead, mercury, arsenic. I mean, really, how useful is that list?
HIV	Direct effect of the virus on nerves.
Paraneoplastic	Can so slow, but probably pretty rare.
Autoimmune – Sjogren’s, sarcoid	Sjogren’s hammers the dorsal roots, so leads to very disabling sensory ataxia. Usually, a whole load of other symptoms (sicca, joint pain). Sarcoid – will what doesn’t it do?

Chronic motor/mixed neuropathies

Chronic motor or mixed neuropathies make up another healthy chunk of outpatient neurology work.  Some of these conditions have already been discussed.

Multifocal motor neuropathy (with conduction block) is a rare, treatable autoimmune condition.  It can present, and indeed mimic, motor neurone disease.  Whilst not exactly “core” knowledge, it does form part of the differential for motor neurone disease presentations.  It is extremely difficult to diagnose confidently, even with repeated nerve conduction studies.

It is beyond the scope of this website, or indeed of the author, to give you chapter and verse on the hereditary neuropathies.  There are endless publications, and the list seems to be ever expanding.

For your exams, it would probably suffice to know a little bit about Charcot-Marie-Tooth (CMT). This is probably not as uncommon as you might expect.  It can present in adulthood and is one of the reasons why taking a family history of “strange feet” and “funny walks” is often surprisingly informative.

Examination reveals distal wasting, pes cavus and absent reflexes.  Sensory abnormalities are the norm.

CMT 1 is a predominantly demyelinating neuropathy;  CMT 2 is predominantly an axonal neuropathy.

The diagnosis can be made both with nerve conduction studies and with genetic analysis.  Patterns of inheritance very and, once again, I would refer you to my esteemed colleague Prof Google.

Chronic motor/mixed neuropathies	Top Tips
CIDP	See above
MMN	Rare. Often exquisitely responsive to IVIG. Look for dropped pinkie and ring fingers. Can look very like MND – hence the paranoia of missing this diagnosis
Hereditary	CMT types 1 – 1,000,000 (or at least it seems that way). Basically, type 1 shows slow conduction in nerve studies (demyelinating) and type 2 shows low amplitudes (axonal). I imagine you could make a career out of this stuff!
Paraprotein neuropathies	Neuropathy associated with paraprotein – I’m sure there is more to say but I can’t carry on…

Autonomic

Basically, sometimes the autonomic nerves come in for a preferential battering. Usually, this is caused by diabetes and amyloidosis. Look for gastroparesis, incontinence, orthostatic hypotension, sweating changes, skin changes.

What are the main problems faced by patients?

The symptoms depend entirely on the type of nerve affected and the location of the nerves themselves.

For example, involvement of the motor nerves leads to weakness. Wasting is invariably present, although is more profound when the motor axon is damaged.  The textbooks will try and tell you that weakness is distal.  This very much depends on the type of neuropathy and this pattern and cannot be relied upon in clinical practice.

Sensory involvement leads to numbness, tingling, impaired temperature sensation and pain.

Autonomic involvement leads to a variety of symptoms, as already mentioned.

Gait and balance our often impaired.  Motor weakness leads to a high-stepping gait, due to foot drop.  Patients can often trip up due to this weakness and many will report feeling unsteady.  Sensory loss can also lead to unsteadiness.  This is worse with the eyes closed or in dim light.

If the upper limbs are also involved, then tasks requiring manual dexterity become much more difficult.

As you can see, the main impact is likely to be on day-to-day activities, although nocturnal pain can lead to severe sleep deprivation.

How do we diagnose it?

Clinical examination

Look for skin changes and wasting on clinical inspection. Tone will be normal and power reduced in a variety of patterns.  The real clincher in this situation is a loss of reflexes.  It is vital that you become proficient in testing reflexes as a student and junior doctor.  Although a small proportion of the general population are areflexic, if a patient has lost a particular reflex, or a whole range of reflexes, then this is usually pathological.  It is a very helpful localising feature and can save you days of pointless investigation whilst waiting for scans that will never help you.

Sensory examination is generally useless.  If your patient is describing a particular pattern of sensory disturbance, then it is likely that you will find this when you examine them.  Why not save yourself some time and just believe them?

If you have to perform a sensory examination, do your best to make it brief.  The more time you spend examining the sensory system the less help it gives you.  Why not have a look at the video in the “How to examine…” part of the website for more details.

Basic tests

A simple haematological and biochemical screen is necessary, although rarely terribly useful.  Here is a list of tests that most neurologists would entertain.

• FBC – looking for raised MCV of B12 or booze
• ESR/CRP – looking for inflammation suggestive of autoimmune neuropathies, myeloma
• Biochemistry – looking for anything that might alarm you
• Immunoglobulins and PPE – looking for myeloma
• HIV
• Autoimmune screen
• B12
• TSH

I have not really mentioned folate anywhere, quite deliberately.  Folate deficiency is uncommon and does not generally lead to any neurological problems.

Given that underlying cancer and sarcoidosis can also cause neuropathy, I typically organise a chest x-ray as part of my basic workup.

Genetic tests

Genetic tests can be useful, particularly if there is a strong family history.  It is beyond the scope of this article to give you chapter and verse but a reasonable starting point, if you suspect CMT is to look for a mutation in the PMP22 gene.

Nerve tests

Nerve conduction studies and EMG can be extremely helpful, particularly if you are trying to work out if the are the is axonal or demyelinating. Look for slow conduction velocities in a demyelinating neuropathy and low amplitudes in an axonal neuropathy.

There are loads of other really “nerdy” things that you can find on the conduction studies but it would take a more intelligent person than I to explain them to you in a way that either of us would understand.

LP

Lumbar puncture is not done terribly often but can be very helpful in acute and sub-acute presentations.  If the CSF protein is elevated then something immunological or infiltrative is likely to be happening.  An “active” CSF, with elevated white cells is also suggestive of something nasty afoot.

Lumbar puncture is rarely undertaken for the more chronic presentations.

Biopsy

Nerve biopsy is a bit of a last resort.  Typically, we will biopsy the sural nerve in the foot.  This is a sensory nerve and, hopefully, your patient won’t miss it much. In my limited experience, nerve biopsy is generally not terribly helpful.

What is the differential diagnosis?

If it isn’t neuropathy, what is it? Alas, for you, and your patients, lots of things can mimic neuropathy.

Here is a little table to get you started.

Condition	Top Tips
Spinal cord – inflammation; vascular event	Usually have a sensory level. Bladder and bowel are often affected too (this is unusual in neuropathies). Upper motor neurone features in true spinal cord lesions – increased tone, enhanced reflexes. Cauda equina and conus medullaris lesions can look very like a neuropathy, so beware …
MND	If there are prominent sensory symptoms, then it is not MND. That bit is pretty easy. Watch out for slowly progressive motor deficits as these can easily be mistaken for neuropathy when the real diagnosis is MND. Prominent fasciculation is unusual in neuropathy.
Nerve root disorders	These are often patchy, painful and due to degenerative disease of the spine. They are rarely the explanation for diffuse weakness. Malignancy can pick off nerve roots and present in a progressive manner.
Myasthenia gravis	Fatigue and weakness can obviously occur in both but prominent diurnal variation is suggestive of neuromuscular weakness. It is a pure “motor” disorder. Reflexes are normal. Can catch out even the most experienced neurologist.
Muscle disease	Usually proximal weakness (but not always) and no sensory loss. Reflexes are normal.
Electrolyte disturbance – low potassium	You should pick this up by accident, if you do your basic blood tests. Hypokalaemia can definitely present with motor weakness. Often caused by medication – diuretics the main culprits

How do we treat it?

Treating neuropathy obviously depends on the underlying cause.

We spend quite a while trying to find a potentially reversible explanation although, more often than not, no such cause is found. If there is a toxic or metabolic insult, then this needs to be addressed.

Immune-mediated, inflammatory neuropathies tend to respond fairly well to high-dose steroids, IVIG or other immunosuppressants (azathioprine, mycophenolate, cyclophosphamide etc.). There are obviously major risks to long-term immunotherapy, and so a careful risk vs benefit discussion is needed before starting.

Don’t forget to refer on for physiotherapy and occupational therapy. In addition, foot-drop splints can be really helpful.